tbuckley/cabot-search huggingface dataset:
Efficacy analysis of CDK4/6 inhibitors (CDKi) + endocrine therapy (ET) treatment in hormone receptor-positive/HER2-negative (HR+/HER2-) advanced breast cancer (aBC): Biomarker analysis including chemoendocrine score (CES) by CDKi type in SOLTI-1801_CDK-PREDICT study.
Authors: Pablo Tolosa Ortega, Tomás Pascual, Cristina Hernando, Sonia Servitja, María Fernández-Abad, Fara Brasó-Maristany, Javier David Benitez Fuentes, Laura Lema, Lucia Parrilla Rubio, Yolanda Ruano, Ana María Roncero, Rodrigo Sanchez-Bayona, Manuel Alva Bianchi, Guillermo Villacampa, María Ángeles Cobos-Fernández, María del Rocío Moreno, Jordi Canes, Fernando Salvador, Aleix Prat, Eva M Ciruelos
Journal: Journal of Clinical Oncology (2023)

1065 Background: CDKi + ET improved progression-free survival (PFS) and ribociclib also overall survival (OS) in HR+/HER2- aBC first-line setting. Intrinsic subtypes (IS) are prognostic and predict benefit from CDKi + ET (Finn. SABCS 2017, Prat. JCO 2021, Tolosa. SABCS 2022). We previously reported a PAM50-based CES in HR+/HER2-negative early BC (Prat et al. CCR 2016). Here, we evaluated the association of CES with PFS following CDKi therapy in aBC. Methods: CDK-PREDICT prospectively evaluated 113 HR+/HER2- aBC patients (pts) treated in the first-line setting with CDKi + ET. RNA from FFPE metastatic tumors was analyzed at the nCounter (Nanostring Technologies) using a 72 custom gene panel including the PAM50 genes. CES was evaluated as a continuous variable, and categorically (CES-E[endocrine-sensitive], CES-I[intermediate] and CES-C[chemo-sensitive]) using the previously reported cut-offs. Multivariable analyses were used to test CES association with PFS. Results: The median follow-up for PFS was 18.5 m. PAM50 IS and CES distribution are shown. No statistically significant difference in mPFS by CDKi. CES (as a continuous variable or as group categories) was found significantly associated with mPFS. mPFS for CES-E pts was NR (95% CI: 26.0 - NR), 20.7m for CES-I (95% CI: 14.2 – 31.7m; HR= 1.98, p&lt;0.05) and 11.7m for CES-C (CI 95%: 7.0 - 18.8; HR= 3.72, p&lt;0.05). CES-C was associated with lower PFS compared to CES-I (aHR= 0.55, p=0.10) and CES-E (aHR= 0.29, p&lt;0.05) independent of CDKi, ET, intrinsic subtype (Luminal versus not), endocrine sensitivity, onset metastatic and visceral disease. CES-C was significantly associated with higher expression of, MIA and lower expression of CCND1, CCNE1, FOXA1, MLPH and UBE2T compared with CES-E (p&lt; 0.05). In CES-E pts mPFS for palbociclib was NR (IC95:22.9-NR) compare with 43.8 m for ribociclib (IC95: 12.0-NR); aHR=1.17 p=0.546), in CES-I pts mPFS for palbociclib was 18.9 m (IC95: 5.8-27.3) compare with 31.7 m for ribociclib (IC95: 12.2-NR); aHR=0.50 p=0.294), and in CES-C pts mPFS for palbociclib was 11.6 m (CI95: 2.7-15-7) compare with 10.0 m for ribociclib (CI95: 2.1-NR; aHR=0.48 p=0.102). Abemaciclib not reported due to low numbers (n=16). Conclusions: We confirmed independent prognostic value of CES in first-line setting, suggesting a not statistically significant benefit with ribociclib vs palbociclib in CES-I. [Table: see text]
Pattern of molecular testing among US veterans with gastrointestinal cancers: A single center experience.
Authors: Sufana Shikdar, Christopher Gentry, Alisha Nicholson, Ravindranauth Sawh
Journal: Journal of Clinical Oncology (2023)

e13663 Background: In response to the rising global burden of cancers, the Veterans Health Administration's (VHA) National Precision Oncology Program (NPOP) supports the use of molecular testing (MT) among veterans. The Oklahoma City (OKC) VHA is serving patients with cancer in both rural and urban areas by implementing the standard practice of precision oncology testing across our diverse patient population. Identification of molecular biomarkers can facilitate treatment selection and trial access for veterans. Here we report real-world practices of physicians caring for veterans with gastrointestinal (GI) cancers namely gastroesophageal (GE), pancreatobiliary (PB) and colon cancers at OKC VHA and determine the degree to which molecular data is being utilized to prognosticate or alter clinical management. Methods: Patients presenting to the OKC VHA with metastatic GE, PB and colon cancer from June 2020 to September 2022 were included in the study. Data was collected retrospectively, including patient demographics, clinical characteristics, mutational data, actionability (OncoKB), and treatment recommendations. The primary outcome was the percentage of tumor sequencing performed, and actionable alteration annotated by the OncoKB database therapeutic evidence level. Results: 101 veterans were diagnosed with metastatic GI cancers (GE 18.8%, PB 28.7% and colon 52.4%), of which 82 samples (81.2%) were submitted for MT. The cohort was male-dominant (98%) with a median age of 69.5 years, and 46.5% of the veterans were from rural Oklahoma. Time from test order date to test result availability was 11.7 days. 25.7% (n=26) had at least one likely oncogenic mutation according to the OncoKB database, and 12.8% of them (n=13) were changed to FDA-approved targeted medications. The most common aberrant genes were TP53, KRAS, HER2, and MSI-H. Statistically significant differences were seen in the level of evidence by cancer group. In multivariate logistic regression, patients with colon cancer were most likely to receive MT (OR, 45.5 95% CI 2.27, 27.0 for colon over PB; OR 14.7 95% CI 2.27, 29.6 for GE over PB). Provider level (fellow vs faculty) and distance from the VHA (urban vs rural) were not associated with MT. Conclusions: Our study indicates clinical implementation of precision oncology is feasible across the VHA healthcare system, including rural veterans. Further analysis of this large cohort of patients will help to address gaps in MT for veterans with GE and PB cancers. The study also highlights the importance of MT to guide clinical trial enrollment and identify investigational drug opportunities among veterans.[Table: see text]
Correlation of gene signatures of Kaiso and LC3A/B protein expression with distinct tumor ecosystems and to predict response to breast cancer therapy.
Authors: Sandeep K. Singhal, Kevin Gardner
Journal: Journal of Clinical Oncology (2023)

566 Background: The multifunctional transcriptional repressor, Kaiso, is a member of the BTB/POZ (Broad complex, Tramtrak, Bric `aBrac/Pox zinc finger) family of zinc finger proteins. Kaiso protein levels in both the nucleus and the cytoplasm have each been shown to be highly sensitive and independent predictors of overall breast cancer survival. Through the use of gene signatures and/or gene modules developed through the analysis of RNA-seq data from breast cancer patients following biomarker stratification by either nuclear Kaiso, cytoplasmic Kaiso, or the Kaiso’s functional downstream target LC3A/B, we demonstrate the utility of Kaiso and LC3A/B derived signatures as predictors of treatment outcome. Methods: We used a machine Learning approach to assess a cohort of racially diverse 555 BC patients who underwent surgery for their primary BC in Greenville, NC and develop proteomics-based genomics (PbG) signatures. The cross-validated logistic regression modeling using publicly available gene expression data compiled from neoadjuvant clinical trials (N=996, JCO:30(16):1996-2004). Results: Kaiso and LC3A/B derived gene modules show accuracy in predicting pathological complete response (pCR, AUC = 0.728, 95% CI: 0.689-0.764). Moreover, predictive estimates of distant metastasis-free survival utilizing Kaiso and LC3A/B derived gene modules are also significant (overall DMFS, AUC= 0.737, 95% CI: 0.665-0.819) and (DMFS of non-pCR patients AUC= 0.71, 95% CI: 0.633-0.773). We then validate these findings in an independent, racially diverse breast cancer cohort receiving neoadjuvant treatment (N=443). Gene modules based on Kaiso and LC3A/B were also highly predictive in this independent cohort (total cohort pCR, AUC= 0.775, 95% CI: 0.687-0.838; pCR NHW (N=257), AUC= 0.762, 95% CI: 0.659-0.855; pCR Hispanic (N=125), AUC= 0.725, 95% CI: 0.493-0.873; and pCR NHB (N=42), AUC= 0.681, 95% CI:0.405-0.904). Conclusions: Combined analysis by multiplex immunofluorescence and deconvolution of gene expression data show that the protein expression of Kaiso and LC3A/B in tumors are associated with distinct tumor ecosystems where high levels cytoplasmic Kaiso are linked to an immune-suppressed tumor microenvironment.
10-year mastectomy trends among breast cancer phenotypes: A national cohort study.
Authors: Matthew Lewis Pierotti, Christian X. Cruz Pico, Jill S Hasler, Austin David Williams, Elizabeth A. Handorf, Allison A. Aggon, Mary Pronovost, Andrea S Porpiglia, Mahtab Vasigh, Richard J. Bleicher
Journal: Journal of Clinical Oncology (2023)

584 Background: Breast cancer tumor phenotype has prognostic value with triple negative (TN) cancers having higher rates of distant metastases early. While tumor phenotypes are prognostic, published data demonstrates that the choice of local therapy does not affect this predisposition or affect survival. This study was performed to determine whether mastectomy is being performed more frequently for TN or HER2+ phenotypes, relative to hormone receptor positive (HR+) phenotypes despite the lack of benefit this should provide. Methods: Data from the National Cancer Database (NCDB) was analyzed from 2010 through 2019 to assess mastectomy trends and associations with patient and tumor characteristics. Women with invasive breast cancer were included. Women with Stage IV disease were excluded. Patients were categorized as mastectomy or breast conservation surgery. Patient and tumor characteristics were compared across groups using chi-square and Wilcoxon rank sum tests, and a multivariable logistic regression model was fit to assess the association between mastectomy and tumor phenotype controlling for patient and tumor characteristics. Results: 543,590 patients were evaluated. 173,380 (31.9%) patients underwent mastectomy, and 370,210 (68.1%) patients underwent breast conservation surgery. Mean age at diagnosis was 56. There were 425,174 HR+, 64,960 HER2+, and 53,456 TN tumors. The proportion of patients undergoing mastectomy peaked in 2013 at 36.14% before declining. Compared to HR+, HER2+ patients were more likely to undergo mastectomy, OR 1.39 p &lt; 0.0001 (95% CI 1.35 – 1.43); however, there was no significant difference in mastectomy between HR+ patients and TN patients. Compared to whites, black patients were less likely to undergo mastectomy, OR 0.71 p &lt; 0.0001 (95% CI 0.69 – 0.74), and individuals of Hispanic ethnicity less likely to undergo mastectomy, OR 0.92 p &lt; 0.0001 (95% CI 0.89 – 0.95). Compared to private insurance, Medicare had a greater association with mastectomy, OR 1.2 p &lt; 0.0001 (95% CI 1.18 – 1.23). There was no significant difference between other forms of insurance (Medicaid, other government insurance, no insurance) and private insurance. Education and income were not associated with different frequencies of mastectomy. Patients with higher comorbidity scores were more likely to undergo mastectomy. Conclusions: Mastectomy rates have been declining since 2013 at CoC centers. While TN breast cancer is not associated with increased mastectomy percent, mastectomy continues to be performed more frequently for HER2+ positive phenotype when adjusting for tumor and patient characteristics. These data suggest a need for education about HER2 positive phenotype due to a possible lack of understanding about the why such tumors pose a risk, and the role of local therapy in treating them.
Time to initial review by oncology clinical pathways committees for new FDA approvals/label expansions.
Authors: Christine L. Caranfa, Joanna Addonizio, Belinda Desravines, Daniel Rezaee, Omar Waid, Joanna M. Hamilton, Victoria H. Selesnick, Michael Scalzo, David Michael Jackman
Journal: Journal of Clinical Oncology (2023)

e13523 Background: Dana-Farber Cancer Institute’s (DFCI) clinical pathways provide expert oncology decision-support. We schedule 2-4 reviews/year for each of over 40 medical oncology pathways, plus ad hoc reviews. When FDA issues new approvals or label expansions, the relevant medical director assigns it to the next scheduled review or a more urgent ad hoc meeting. Here we explore the time to initial review (TTIR) for FDA approvals. Methods: This analysis includes FDA approvals/label expansions for adult oncology patients from 01/01/2021 – 12/31/2022. We excluded CAR-T therapies as well as FDA approvals not directed at one of our existing pathways. TTIR was calculated from date of FDA approval to date of DFCI clinical pathways review. Univariate analyses examined the impact of prior in-class competitors in the specific approval setting; prior approvals for the treatment class in general; and scheduled meeting cadence. Results: From January 1, 2021 – December 31, 2022, there were 58 FDA approvals/label expansions in diseases for which a DFCI pathway exists. Eighteen represented items that had been previously addressed (e.g., conversion of accelerated approval to full, or a label expansion adopted into pathways earlier based on published data). For the remaining 40 new approvals or label expansions, the median TTIR was 3.4 months. 43% of FDA approvals were addressed prior to or within 30 days after announcement. There were 9 ad hoc reviews over this period, including review of 3 new FDA approvals. Median TTIR for items that were a first-in-class therapy for that specific indication (n= 20) was 2.1 months, compared to 3.5 months for agents with an existing in-class competitor in that setting (n=20). Median TTIR for items that represented the first approval for a novel first-in-class agent (n=13) was 1.5 months; TTIR for agents with existing in-class approvals in any setting (n=27) was 3.5 months. Median TTIR for FDA actions involving diseases/pathways that have &gt; 3 scheduled review meetings/yr (n=28) was 2.8 months, compared to 5.2 months in pathways with 1-2 scheduled reviews/yr (n=12). Conclusions: Clinical Pathways provide a structured mechanism for reviewing whether, when, and how new treatments are best used in oncology practice, and for disseminating those recommendations to providers. The time to initial review was shorter for initial registrational approvals for novel agents, and for treatments in diseases with more frequent meetings. [Table: see text]
Longitudinal MRI-based fusion novel model to predict pathological complete response in breast cancer treated with neoadjuvant chemotherapy: A multicenter, retrospective study.
Authors: Kun Wang, Yuhong Huang
Journal: Journal of Clinical Oncology (2023)

599 Background: Accurate identification of pCR to neoadjuvant chemotherapy (NAC) is important for determining appropriate surgery strategy and guiding the resection extent in breast cancer. However, a non-invasive tool to predict pCR accurately is lacking. Our study aims to develop ensemble learning models using longitudinal multiparametric MRI to predict pCR for each molecular subtype of breast cancer. Methods: In this study, all patients underwent pre-NAC and post-NAC MRI examinations, and we collected multiparametric MRI sequences. Post-operation pathologic results were used to determine the pathologic complete response (pCR). We extracted 14676 radiomics and 4096 deep learning features and calculated a set of additional delta-value features. Then in the primary cohort (n = 409), inter-class correlation coefficient test, U-test, Boruta and the least absolute shrinkage and selection operator (LASSO) regression were used to select the most optimal feature set for each subtype of breast cancer. Finally, 20, 15 and 13 features were selected to construct the models based on 5 specific algorithms with cross-validation method for predicting pCR in HR+/HER2-, HER2+ and TNBC subtypes. The ensemble learning strategy was used to integrate the single-modality models outputs and improve the prediction performance. The diagnostic performances of models were evaluated in the three external cohorts with lager sample size of patients (n = 343, 170 and 340, respectively). Results: A total of 1262 patients with breast cancer from four centers were enrolled in this study, and pCR rates were 10.6% (52/491), 54.3% (323/595) and 37.5% (66/176) in HR+/HER2-, HER2+ and TNBC subtype. After model development, the Multi-Layer Perception (MLP) neural network yields the best diagnostic performances in all subtypes and feature sets. In the three subtypes, the stacking model integrating pre-, post- and delta- models yielded the highest AUCs of 0.959, 0.974 and 0.958 in the primary cohort, and AUCs of 0.882-0.908, 0.896-0.929 and 0.837-0.901 in the three external validation cohorts, respectively. In all subtypes, the stacking model had accuracies of 85.0%-88.9%, sensitivities of 80.0%-86.3%, and specificities of 87.4%-91.5% in the external validation cohorts. Conclusions: Our study established a novel tool to predict the responses of breast cancer to NAC and achieve excellent performance. The models could help to determine post-NAC surgery strategy for patients with breast cancer.
Analysis of pathological complete response (PCR) and impact of modifiable risk factors on the premature discontinuation of pertuzumab use in early stage HER-2 breast cancer: A retrospective single-institutional study.
Authors: Khurram Anwar, Jai Kumar Khatri, Mohd Masoudi, Mahmoud Abdallah, Ihab Tahboub, Kemnasom Nwanwene, Eldib Howide, Maria Rosalia Tria Tirona
Journal: Journal of Clinical Oncology (2023)

e12627 Background: In patients with HER-2 positive breast cancer, Pertuzumab in combination with Trastuzumab forms a potent Anti HER-2 regimen. Randomized clinical trials have concluded that addition of Pertuzumab to Trastuzumab and Chemotherapy leads to improved rates of Pathological Complete Response and also improved Invasive-disease-free survival rates in early stage HER-2 positive breast cancer. Pertuzumab is frequently associated with treatment limiting diarrhea and other adverse effects. In this study, we report our experience with the use of Pertuzumab in early stage HER-2 breast cancer. We analyzed the adverse events, PCR rates for those patients who had premature discontinuation of treatment versus those who had successful treatment completion, and modifiable risk factors that may have affected completion of treatment. Methods: We conducted an IRB approved, retrospective study, analyzing the use of Pertuzumab at our institution for early stage (Stage I-III), HER-2 positive female and male breast cancer patients seen from June 2018 to June 2022. Data were obtained from our Institutional Cancer Registry. Results: One hundred and eighteen (118) patient charts were reviewed. Sixty Five (55.08%) patients received Pertuzumab. Of the patients who received Pertuzumab, 61 (93.85%) received it in the Neoadjuvant setting. Thirty Eight (58.46%) patients completed the treatment and 27 (41.5%) patients had premature treatment discontinuation due to adverse effects. The rate of PCR in patient who completed the prescribed treatment course was 55.56%, and 51.85% for those who did not (p value 0.77). Among the patients in whom treatment was discontinued, diarrhea (51%), followed by rash (11.11%) were the main adverse effects. Almost 66% of non-smokers completed treatment as compared to 48% of smokers (p value 0.15). Patients with a normal BMI had a treatment completion rate of 76% compared to obese or overweight patients who had a rate of 52% (p value 0.08). Conclusions: Our retrospective study showed that there was a high premature discontinuation rate of the use of Pertuzumab. This is due to adverse effects, diarrhea being the most notable. However, the PCR rate difference was not statistically significant (55.56 vs 51.85, P value 0.77) in patients who completed treatment versus those who did not. There was a positive trend observed that non-smokers and non-obese patients were more likely to complete treatment with Pertuzumab. Although it was observed that premature discontinuation of Pertuzumab did not significantly impact PCR, further studies are required to validate this observation.
Development and validation of a NCC-BC-A scale to assess patient-reported outcomes for advanced breast cancer patients in China.
Authors: Xiuwen Guan, Fei Ma, Xiaoyan Yan, Tianmou Liu, Ning Shen
Journal: Journal of Clinical Oncology (2023)

e13125 Background: The primary therapeutic objectives for advanced breast cancer (ABC) are to extend patients’ survival time and to maintain their quality of life (QoL). Patient-reported outcomes (PROs) symptom could improve communication with physicians, and decreased utilization of unplanned healthcare. However, localized PROs scales for ABC were seldomly used in China. This study aimed to develop a specific PROs scale for ABC patients in China and optimize the management model for breast cancer. Methods: A literature search was conducted in PubMed, Embase, Wanfang, and CNKI databases, and the dimensions and items of the scale in the literature were extracted for the item pool. Delphi method was used to modify, add, subtract, and adjust the language of scale items until the experts' suggestions or opinions reached a consensus, and the first draft of the scale was formed. The first draft of the scale was further optimized by cognitive test and pre-survey. The optimized scale was used for formal survey, and the items of the scale were further analyzed and screened by coefficient of variation, correlation coefficient, internal item consistency, factor analysis, reliability, and validity. All tests were two-sided tests, and the test level was α=0.05. Results: A total of 10945 articles were analyzed, and 237 were finally included to form an item pool containing 277 PRO items. Two rounds of Delphi expert consultation were conducted, and the average authority coefficient of experts was Cr&gt;0.7. Based on the results of cognitive test, the corresponding items were revised by language description to facilitate understanding. After adjustments according to the pre-survey of 200 ABC patients, the PROs scale NCC-BC-A was finally formulated with a total of 38 items, including 9 physiological dimension items, 4 psychological dimension items, 9 social dimension items, 11 treatment-evaluation items, 4 overall self-evaluation dimension items, and 1 other dimension. A total of 588 ABC patients participated in the national formal survey of NCC-BC-A with the average answer time of 6 minutes, and no floor or ceiling effects were observed. A series of statistical tests were conducted on the result. A principal component analysis revealed that the items in PROs scale have great consistency while preserving enough differences between different dimensions. The results were tested to be normally distributed with good variation. Also, the PROs scale survey result has an excellent Cronbach's α coefficient of 0.925 and an excellent test-retest reliability of 0.9041. Conclusions: The PROs scale NCC-BC-A has high validity and reliability, can objectively measure the QoL of ABC patients. NCC-BC-A fully considered the characteristics of treatment status for ABC patients, and the realistic situation in China, which may help clinicians to pay more attention to QoL of ABC patients and to optimize management system for ABC.